Aims: We are planning a clinical trial in which we randomly assign and then observe infants on soy formula with and without soy estrogens to see if their exposure to soy estrogen prolongs anatomical and biochemical evidence of estrogen exposure and response. The time course of these findings in infants is not well characterized, and detailed planning of the trial will require a substantial amount of pilot work.. Plausible effects include 1) anatomic expression of estrogen activity: breast buds, labial size, vulval anatomy, scrotal rugae, and, by ultrasound, small ovarian cysts and possibly prostate volume and 2) biochemical evidence of activity: decrease in gonadotropins, decrease in estrone/estradiol synthesis. We have begun planning the pilot studies. Term newborns have anatomic and sonographic evidence of in utero estrogen exposure. Over the first 6 months to a year of life, as the influence of maternal hormone wanes, these findings recede. Soy infant formula contains large amounts of isoflavones (daidzein and genestein) that can occupy estrogen receptor and act as estrogens in the laboratory. Circulating isoflavones in infants fed soy formula are at serum concentrations 3 or 4 orders of magnitude higher than estradiol, so that even if they are weak and readily excreted, there is so much that they should be active. Anatomic, sonographic, and other biochemical evidence of estrogen exposure have not been looked for in infants fed soy. Limited clinical trial data show increases in cholesterol synthesis consistent with an estrogen effect in infants fed soy formula vs. human milk or cow milk formula. An estrogen source in the diet might prolong the effect of maternal hormones, or interfere with hormonal homeostasis in the child. Accomplishments: This project is in the planning stage. We have reviewed the literature, contructed a preliminary protocol, completed external review, and has a planning meeting with outside experts.